Viral regulatory complexes perform critical functions and are important targets for therapeutic intervention. In HIV, the Tat and Rev proteins form regulatory complexes with multiple viral and cellular factors to direct transcription and export of the viral RNA.
Rev is a 116 amino acid RNA binding protein that is expressed early in the life cycle of the virus. Rev binds the Rev Response Element (RRE), a highly structured 270 nt RNA element encoded within the env gene. Current models suggest that six Rev molecules bind the RNA in order to properly position two of the nuclear export sequences on Rev for binding to a dimer of the Crm1-RanGTP export complex. This complex is then exported through the nuclear pore and the complex disassembles allowing for translation of the late HIV proteins and packaging of the viral genome. Identifying compounds which may provide interference with any of these interactions thus preventing the formation of a competent export complex is a challenge. Provided herein are solutions to these and other problems in the art.